Prolonged contact with dendritic cells turns lymph node‐resident NK cells into anti‐tumor effectors
Year: 2016
Type: article
Abstract: Natural killer (NK) cells are critical players against tumors. The outcome of anti-tumor vaccination protocols depends on the efficiency of NK-cell activation, and efforts are constantly made to manipulate them for immunotherapeutic approaches. Thus, a better understanding of NK-cell activation dynamics is needed. NK-cell interactions with accessory cells and trafficking between secondary lymphoid organs and tumoral tissues remain poorly characterized. Here, we show that upon triggering innate immunity with lipopolysaccharide (LPS), NK cells are transiently activated, leave the lymph node, and infiltrate the tumor, delaying its growth. Interestingly, NK cells are not actively recruited at the draining lymph node early after LPS administration, but continue their regular homeostatic turnover. Therefore, NK cells resident in the lymph node at the time of LPS administration become activated and exert anti-tumor functions. NK-cell activation correlates with the establishment of prolonged interactions with dendritic cells (DCs) in lymph nodes, as observed by two-photon microscopy. Close DC and NK-cell contacts are essential for the localized delivery of DC-derived IL-18 to NK cells, a strict requirement in NK-cell activation.
Source: EMBO Molecular Medicine
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: Crohn's and Colitis Foundation of America, Harvard University, Crohn's and Colitis Foundation, Fondazione Cariplo, Associazione Italiana per la Ricerca sul Cancro, Fondazione Regionale per la Ricerca Biomedica, National Institutes of Health, Harvard Digestive Diseases Center, Harvard University, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1465509803, Generation and Function of NK Cell Memory, G4788905788, Role of the NFAT signalling pathway in determining inflammation during aging and neurodegeneration, G5857948765, G6272639891, G6325015508, G6938688542, Study of the role of CD14-dependent signaling pathways during sepsis, Multifunctional gold nanoparticles as a platform for new carbohydrate-based vaccines - NANOVAC, Integrated Epithelial and Muscosal Biology, Innate control of the inflammatory process during fungal infections
OpenAlex ID: W2473097366